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Differential effect of immune cells on non‐pathogenic Gram‐negative bacteria‐induced nuclear factor‐κB activation and pro‐inflammatory gene expression in intestinal epithelial cells
Author(s) -
Haller D.,
Holt L.,
Parlesak A.,
Zanga J.,
Bäuerlein A.,
Sartor R. B.,
Jobin C.
Publication year - 2004
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2004.01874.x
Subject(s) - immune system , gram negative bacteria , bacteria , biology , gene expression , gene , differential (mechanical device) , gram , microbiology and biotechnology , inflammation , pathogenic bacteria , immunology , escherichia coli , genetics , physics , thermodynamics
Summary We have previously shown that non‐pathogenic Gram negative bacteria induce RelA phosphorylation, nuclear factor (NF)‐κB transcriptional activity and pro‐inflammatory gene expression in intestinal epithelial cells (IEC) in vivo and in vitro . In this study, we investigated the molecular mechanism of immune‐epithelial cell cross‐talk on Gram‐negative enteric bacteria‐induced NF‐κB signalling and pro‐inflammatory gene expression in IEC using HT‐29/MTX as well as CaCO‐2 transwell cultures Interestingly, while differentiated HT‐29/MTX cells are unresponsive to non‐pathogenic Gram negative bacterial stimulation, interleukin‐8 (IL‐8) mRNA accumulation is strongly induced in Escherichia coli ‐ but not Bacteroides vulgatus ‐stimulated IEC cocultured with peripheral blood (PBMC) and lamina propria mononuclear cells (LPMC). The presence of PBMC triggered both E. coli ‐ and B. vulgatus ‐induced mRNA expression of the Toll‐like receptor‐4 accessory protein MD‐2 as well as endogenous IκBα phosphorylation, demonstrating similar capabilities of these bacteria to induce proximal NF‐κB signalling. However, B. vulgatus failed to trigger IκBα degradation and NF‐κB transcriptional activity in the presence of PBMC. Interestingly, B. vulgatus ‐ and E. coli ‐derived lipopolysaccharide‐induced similar IL‐8 mRNA expression in epithelial cells after basolateral stimulation of HT‐29/PBMC cocultures. Although luminal enteric bacteria have adjuvant and antigenic properties in chronic intestinal inflammation, PBMC from patients with active ulcerative colitis and Crohn's disease differentially trigger epithelial cell activation in response to E. coli and E. coli ‐derived LPS. In conclusion, this study provides evidence for a differential regulation of non‐pathogenic Gram‐negative bacteria‐induced NF‐κB signalling and IL‐8 gene expression in IEC cocultured with immune cells and suggests the presence of mechanisms that assure hyporesponsiveness of the intestinal epithelium to certain commensally enteric bacteria.